Multiple Sclerosis (MS) is an unpredictable health condition that affects physical, cognitive, and emotional aspects of life (Compston & Coles, 2008). Emotional adjustment to MS is often studied by examining psychopathology rather than positive adjustment outcomes. Lacking in the literature on adjustment to MS is attention to integrated and parsimonious models of both negative and positive aspects of emotional adjustment. The purpose of this study was to examine, compare, and integrate two models of emotional adjustment to MS, with adjustment conceptualized as including both negative outcomes (i.e., anxiety, depression, negative affect) and positive outcomes (i.e., positive affect and quality of life). Individuals with MS (N = 431) completed questionnaires online to assess the components of Lazarus and Folkman’s (1984) stress and coping model, and a model of Taylor’s (1983) theory of cognitive adaptation, along with multiple outcome measures. Exploratory and confirmatory factor analyses were used to refine the variables for inclusion in the models. Structural equation modelling was used to test the models. The stress and coping model explained a large proportion of variance (98.4%) in negative adjustment outcomes, but was unable to be used to test positive adjustment outcomes. Primary appraisals and escape-avoidance coping were associated with greater negative adjustment, whereas cognitive restructuring and problem solving coping and emotional and social coping were weak contributors to explaining adjustment. The cognitive adaptation model explained a large proportion of variance in both positive (81.9%) and negative adjustment (97.3%). Benefit finding was a weak contributor to positive adjustment but not negative adjustment. The remaining cognitive adaptation variables (i.e., optimism, self-esteem, and mastery) each contributed to the prediction of adjustment outcomes. Model comparison revealed that the cognitive adaptation model provided a better fit for examining adjustment outcomes. The stress and coping model was unsuccessfully integrated with dispositional optimism and the remaining cognitive adaptation components. Multicollinearity of latent variables and suppression in mediation were evidenced in both of the adjustment models. The results contribute to the theoretical study of multiple conceptualizations of emotional adjustment to MS and provide a rare comparison of two adjustment models. This study also leads to valuable information for clinicians.